PrimeC, a combination therapy targeting multiple disease pathways, is designed to slow ALS progression by modulating inflammation, oxidative stress, iron metabolism, and microRNA dysregulation.

Evaluating safety, tolerability, and efficacy of PrimeC in people living with ALS (PwALS) through a randomized, placebo-controlled, double-blind Phase 2b trial (PARADIGM; NCT05357950); a 6-month double-blind phase (DB) followed by a 12-month open-label extension (OLE). Primary outcomes are safety, tolerability and key biomarkers, with ALS-progression and other ALS-related biomarkers as secondary and exploratory measures.

Sixty-eight PwALS were randomized 2:1 and received PrimeC for 12 months, or placebo for 6-months followed by 6-months of OLE. Secondary outcomes measured ALSFRS-R, SVC, survival, and QoL. microRNAs and iron-related markers were assessed as exploratory outcomes.

At 12 months, PrimeC treatment attenuated disease progression (ALSFRS-R) by 36%  compared to the placebo-to-PrimeC arm (Mean difference=6.561, 95% CI:1.744-11.378, p=0.009). Survival probability was 43% higher in the PrimeC-treated group compared to the placebo-to-PrimeC group, though this difference did not reach statistical significance (95% CI:0.15-2.17, p=0.41). This effect built upon earlier findings from the DB, where PrimeC slowed disease progression by 29% compared to placebo (Mean difference=2.232, 95% CI:-0.606-5.069; p=0.12). Similar trends were observed across secondary clinical outcomes.

PrimeC modified iron metabolism, significantly reducing pathologically elevated ferritin levels (p=0.18), and increasing transferrin levels (p=0.09). The placebo-to-PrimeC arm showed ALSFRS-R correlations with ferritin (p=0.0019) and transferrin (p=0.097), which were abolished in the PrimeC-treated group. Modulation of microRNA metabolism was demonstrated by 24 differentially-expressed microRNAs in the PrimeC-treated arm, including miR-199a, with no changes in the placebo group.

Findings from the 18-month analysis will be presented at the meeting.

PrimeC demonstrated a statistically significant reduction in ALSFRS-R over 12 months, with a favorable safety and tolerability profile. PrimeC not only slows disease progression and suggests improved survival, but also effectively modulates ALS-related biomarkers, demonstrating strong target-engagement.